蛋白质SUMO化代表重要的细胞过程,其调节许多宿主蛋白质以及许多侵袭性病毒蛋白质的活性。口蹄疫病毒(FMDV)是发现的第一种动物病毒。然而,SUMO化是否在FMDV感染过程中发生以及在FMDV发病机制中的作用尚未研究。在本研究中,我们证明了SUMO化通过小干扰RNA(siRNA)转染抑制FMDV的复制与SUMO化的药物抑制,这进一步证实了在3C蛋白酶突变的SUMO化缺陷型FMDV的病毒复制增加,亚代谢的目标。此外,我们提供了四个赖氨酸残基的证据,Lys-51,-54,-110和-159一起工作,将SUMO化赋予FMDV3C蛋白酶,这可能使FMDV3C的SUMO化更稳定,并提高宿主抑制FMDV复制的机会。这是首次报道可以通过SUMO化选择性修饰四个赖氨酸残基。最后,我们表明SUMO化减弱了切割能力,干扰素信号通路的抑制作用,和FMDV3C的蛋白质稳定性,这似乎与FMDV复制的减少有关。一起来看,我们的实验结果描述了一种新的细胞调节事件,该事件通过3C蛋白酶的SUMO化显著限制了FMDV的复制。重要性口蹄疫是偶蹄动物的高度传染性和经济上重要的疾病。SUMOylation,一种小的泛素样蛋白与多种底物蛋白的共价连接,已成为重要的翻译后修饰,在多种生物过程中起着多种作用。在这项研究中,发现FMDV3C的四个赖氨酸残基被SUMO化选择性修饰。此外,我们证明了SUMO化通过多种机制减弱FMDV3C的功能,包括卵裂能力,干扰素信号通路的抑制作用,和蛋白质的稳定性,which,反过来,导致FMDV复制减少。我们的发现表明,FMDV3C的SUMO化可以作为抵抗FMDV复制的宿主细胞防御。对驱动这一过程的细胞和分子机制的进一步理解应该提供新的见解,以设计一种有效的策略来控制FMDV在动物中的传播。
Protein SUMOylation represents an important cellular process that regulates the activities of numerous host proteins as well as of many invasive viral proteins. Foot-and-mouth disease virus (FMDV) is the first animal virus discovered. However, whether SUMOylation takes place during FMDV infection and what role it plays in FMDV pathogenesis have not been investigated. In the present study, we demonstrated that SUMOylation suppressed FMDV replication by small interfering RNA (siRNA) transfection coupled with pharmaceutical inhibition of SUMOylation, which was further confirmed by increased virus replication for SUMOylation-deficient FMDV with mutations in 3C protease, a target of SUMOylation. Moreover, we provided evidence that four lysine residues, Lys-51, -54, -110, and -159, worked together to confer the SUMOylation to the FMDV 3C protease, which may make SUMOylation of FMDV 3C more stable and improve the host\'s chance of suppressing the replication of FMDV. This is the first report that four lysine residues can be alternatively modified by SUMOylation. Finally, we showed that SUMOylation attenuated the cleavage ability, the inhibitory effect of the interferon signaling pathway, and the protein stability of FMDV 3C, which appeared to correlate with a decrease in FMDV replication. Taken together, the results of our experiments describe a novel cellular regulatory event that significantly restricts FMDV replication through the SUMOylation of 3C protease. IMPORTANCE FMD is a highly contagious and economically important disease in cloven-hoofed animals. SUMOylation, the covalent linkage of a small ubiquitin-like protein to a variety of substrate proteins, has emerged as an important posttranslational modification that plays multiple roles in diverse biological processes. In this study, four lysine residues of FMDV 3C were found to be alternatively modified by SUMOylation. In addition, we demonstrated that SUMOylation attenuated FMDV 3C function through multiple mechanisms, including cleavage ability, the inhibitory effect of the interferon signaling pathway, and protein stability, which, in turn, resulted in a decrease of FMDV replication. Our findings indicate that SUMOylation of FMDV 3C serves as a host cell defense against FMDV replication. Further understanding of the cellular and molecular mechanisms driving this process should offer novel insights to design an effective strategy to control the dissemination of FMDV in animals.